|
 |
| ORIGINAL ARTICLE |
|
| Year : 2021 | Volume
: 22
| Issue : 2 | Page : 108-114 |
|
|
The effect of early aggressive diuresis on hospital length of stay in acute congestive heart failure
Muhammad Butt1, Ahmad Jabri1, Hany Messeh2, Abdullah Ahmed3, Anas Alameh4, Faris Haddadin5, Andin Mullis3, Claude S Elayi6
1 Heart and Vascular Center, Case Western Reserve University/MetroHealth Medical Center, Ohio, USA
2 Department of Internal Medicine, Mercy Hospital of Buffalo, The State University of New York at Buffalo, New York, USA
3 Gill Heart and Vascular Institute, University of Kentucky, Kentucky, USA
4 Department of Internal Medicine, Cleveland Clinic Akron General, Ohio, USA
5 Section of Cardiology, Baylor College of Medicine, Houston, Texas, USA
6 Department of Cardiology, Saint Joseph Hospital CHI Commonspirit, Kentucky, USA
| Date of Submission | 25-Feb-2021 |
| Date of Acceptance | 16-Jun-2021 |
| Date of Web Publication | 19-Aug-2021 |
Correspondence Address:
Dr. Anas Alameh
1-Akron General Ave, Akron 44307, Ohio
USA
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/HEARTVIEWS.HEARTVIEWS_24_20
 Abstract | | |
Background: Diuresis is the mainstay of treatment during hospitalization for patients admitted with congestive heart failure (CHF). Hospital length of stay (LOS) is considered an important patient outcome for CHF patients; previous studies comparing higher rates of diuresis (aggressive) versus relatively lower rates (nonaggressive) on patient outcomes have shown contradicting results. In fact, no specific guidelines to direct diuretic therapy exist. This investigation was designed to study the effect of early aggressive diuresis on hospital LOS.
Methods: Data from 194 CHF patients (admitted to the hospital for 1 year) were collected and analyzed in a retrospective cohort study design. Patients were divided into two cohorts based on urine output achieved in the first 24 h of admission; the aggressive diuresis cohort (urine output ≥2400 mL) comprised of 29 subjects while the nonaggressive diuresis cohort (urine output ≤2400 mL) had 165 subjects. The primary endpoint was LOS.
Results: Median LOS for the aggressive diuresis cohort was 4 days (95% confidence interval [CI]: 2.95–5.06) as compared to 5 days (95% CI 4.40–5.60) for the nonaggressive diuresis cohort; log-rank test showed no significant differences between the hospitalized proportions between the two cohorts over time (P = 0.67).
Conclusion: Hospital LOS for CHF patients treated with early aggressive diuresis was not significantly different compared to patients treated with nonaggressive diuresis.
Keywords: Congestive heart failure, diuresis, hospital length of stay
How to cite this article:
Butt M, Jabri A, Messeh H, Ahmed A, Alameh A, Haddadin F, Mullis A, Elayi CS. The effect of early aggressive diuresis on hospital length of stay in acute congestive heart failure. Heart Views 2021;22:108-14 |
How to cite this URL:
Butt M, Jabri A, Messeh H, Ahmed A, Alameh A, Haddadin F, Mullis A, Elayi CS. The effect of early aggressive diuresis on hospital length of stay in acute congestive heart failure. Heart Views [serial online] 2021 [cited 2023 Dec 5];22:108-14. Available from: https://www.heartviews.org/text.asp?2021/22/2/108/324108 |
| Introduction | |  |
Congestive heart failure (CHF) can be thought of as a pandemic that exerts significant health and economic burden on society.[1],[2] It affects roughly 6.5 million people in the United States and 26 million around the world.[3] Hospitals are particularly affected as CHF patients are frequently admitted requiring a higher level of care;[4],[5],[6],[7],[8] in fact the re-admission rate is estimated to be 25% within 30 days of a recent hospital discharge,[9] adding significant costs to the health care system. It is estimated that the costs of CHF admissions contribute to around 1.5% of the annual health care budget for most Western countries.[10] Hospitals are constantly trying to improve patient outcomes and reduce costs. In the United States, Medicare-based reimbursement for hospitals for managing CHF admissions is tied to various quality measures such as hospital length of stay (LOS) and re-admission rates;[11] hospitals are penalized if they fail to meet standards.[12] The hope is that optimal CHF treatment practices can be discovered so that important patient outcomes such as hospital LOS (US national average hospital LOS is estimated to be between 6–8 days for CHF patients)[13] can be improved and subsequently financial costs can be lowered.
The mainstay of treatment for patients admitted with CHF is diuretics.[14],[15],[16] Clinical improvement results when symptoms of congestion are relieved with diuresis.[17] Symptomatic relief and patient outcomes are directly related to the absolute urine output rather than the dose of diuretics administered. Loop diuretics are considered the primary class of diuretics for CHF.[18],[19]
In clinical practice, factors such as dose, frequency, and route of administration of diuretics vary considerably and optimal diuresis guidelines to direct best practices do not exist.[15] Many clinical studies have been conducted in the past comparing the effect of aggressive versus nonaggressive diuresis strategies on patient outcomes, yielding mixed results.
Previously, the DOSE trial observed the effect of varying doses of diuretics on hospital LOS.[20] Results from the DOSE trial did not show a difference on the overall LOS even when higher doses of diuretics were administered. Other investigations such as Howard and Dunn and Li and Hong showed that aggressive diuresis did indeed lead to a shorter LOS.[13],[21] In the backdrop of such inconsistencies we decided to compare the effect of early aggressive diuresis on hospital LOS against nonaggressive diuresis.
| Methods | | |
Study design and population
We used a retrospective cohort study model. Patients admitted to the medical ward or cardiac care unit with CHF between the years 2014 and 2015 were identified retrospectively using the International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) diagnosis code.
Patients aged between 18 and 80 years who fulfilled the CHF diagnosis criteria with; elevated filling pressures, presence of at least one relevant symptom, and the presence of at least one relevant physical examination finding were included. We did not use the ejection fraction of the heart as part of our inclusion criteria. We included both; initially diagnosed and chronic patients with exacerbation of CHF.
We excluded patients if they had; history of ESRD on dialysis, history of chronic obstructive pulmonary disease, asthma exacerbation on presentation, creatinine >2.0 mg/dl on presentation, cardiogenic shock (defined as systolic blood pressure [BP] <90 mm Hg and requiring hemodynamics support) or acute coronary syndrome on presentation.
Data collection and organization
Each patient was followed for 30 days from the day of admission and relevant data were recorded. Patients were censored if they died during the hospitalization or if they were still admitted till the end of the study period (December 31, 2015).
We collected data for; demographic details, systolic BP on presentation, serum creatinine level on presentation, left ventricle ejection fraction, type of CHF (systolic or diastolic), method of delivery of furosemide in the first 24 h (intravenous bolus or continuous infusion), amount of urine output in the first 24 h of admission (in milliliters), and adverse events (arrhythmias, worsening renal function, hypotension).
We then categorized the patients into two categories; the aggressive diuresis group (urine output ≥2400 mL in the first 24 h) and the nonaggressive diuresis group (urine output ≤2400 mL in the first 24 h).
Endpoint
The primary endpoint was hospital LOS.
Statistical analysis
Study size and power estimates were based on the median number of days of hospital stay using the log-rank test method. Based on 450 admissions in the hospital each year, we expected 90% power. Type 1 error level was chosen as 0.05 for a two-sided hypothesis.
Normally distributed data were presented as mean and standard deviation, while nonnormal data were presented as median and interquartile range (IQR). Categorical data were presented as frequencies and percentages. We cross-tabulated categorical variables with Chi-square test to determine whether the observed distribution fitted the expected distribution when cell size was sufficient. When the cell size was not enough, Fisher's exact test was used. For continuous covariates, independent sample t-test was used to compare the mean between the aggressive and the nonaggressive diuresis groups for normally distributed data, whereas Mann − Whitney U test was used for nonnormal data.
In multiple linear regression model, we defined the predictors of 24-h urine output by regressing the 24-h urine output as a continuous outcome variable on the 24-h furosemide dose.
Cox proportional hazards regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval for hospital discharges in the aggressive versus nonaggressive diuresis groups.
Nonparametric Kaplan Meir method was used to compare the proportion of patients discharged from the hospital between the aggressive and the nonaggressive diuresis groups. Survival curves were compared using log rank and Breslow tests.
Statistical analysis was performed with SPSS version 24.0 and SAS version 9.4 (IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp, and SAS version 9.4.). Significance was defined as the two-tailed value of P < 0.05.
| Results | | |
A total of 483 patients met the screening criteria. Of the 483 patients, we excluded 289 cases, leaving 194 patients. Of the 194, 29 fell into the aggressive diuresis group, while 165 came under the nonaggressive diuresis group [Figure 1]. Follow-up was complete in all cases. Six patients died in the nonaggressive diuresis group and were censored from the final analysis.
In the entire cohort (including both groups), the range of urine output in the first 24 h ranged from 110 to 5800 mL with a mean of 1372 ± 1009 mL. The total furosemide doses administered in the first 24 h ranged from 40 to 240 mg with a median dose of 80 mg (IQR 40–80). The total range of LOS was 1–28 days with a median of 5 days (IQR 3–8).
Distributions of age, sex, race, and types of CHF (systolic or diastolic) were similar between the two groups. The mean of the systolic BP on presentation was higher in the aggressive diuresis group as compared to the nonaggressive diuresis group (144+−23 vs. 135+−23; P = 0.046). The total dose of furosemide administered in the first 24 h was higher in the aggressive diuresis group versus the nonaggressive group (P = 0.049). The mean of the urine output in the first 24 h was higher in the aggressive diuresis group as compared to the nonaggressive group (3209 ± 903 vs. 1049 ± 598; P = 0.001).
The proportion of patients who developed kidney dysfunction was higher in the aggressive diuresis group as compared to the nonaggressive diuresis group, but it was not statistically significant (12.15% vs. 6.9%; P = 0.2). The proportion of patients with an episode of hypotension was higher in the nonaggressive diuresis group as compared to the aggressive diuresis group, but it was not statistically significant (6.9% vs. 13.9%; P = 0.38). Six deaths were recorded in the nonaggressive diuresis group was compared to none in the aggressive diuresis group [Table 1].
The final multivariable linear regression model after backward elimination showed a statistically significant main effect (P < 0.001) of the dose of furosemide in increasing the initial 24 h urine output along with its interaction with serum creatinine at the time of admission [Supplementary Table 1]. A higher dose of furosemide was required to produce the same amount of urine if the serum creatinine on presentation was >1.6 mg/dL [Figure 2]. | Figure 2: Scatter plot with regression line for relationship between total dose of furosemide used in 1st 24 h, urine output in 1st 24 h in patients with ≤1.6 mg/dL and >1.6 mg/dL serum creatinine levels at admission
Click here to view |
In univariate analysis, Cox proportional hazards regression showed that the effect of aggressive diuresis on the unadjusted hazard rate of hospital discharge was not statistically significant (HR = 1.08; P = 0.70) [Supplementary Table 2].
In multivariate analysis, Cox proportional hazards regression showed that the effects of; creatinine at the time of admission when >1.6 mg/dL (P = 0.75), left ventricular ejection fraction (P = 0.14), total 24 h dose of furosemide administered (P = 0.98) and interaction between furosemide and creatinine (P = 0.79), on the risk of hospital discharge were not statistically significant [Supplementary Table 3].
The adjusted hazard rate of discharge from the hospital was 12% higher in the aggressive diuresis group as compared to the nonaggressive diuresis group but was not statistically significant (adjusted HR = 1.12; P = 0.6) Kaplan Meier estimate of the median accumulated proportion of patients still in the hospital in the aggressive diuresis group was 4 days as compared to 5 days in the nonaggressive diuresis group [Table 2]. Log-rank test (P = 0.67) and Breslow test (0.77) showed no significant differences between the accumulated hospitalized proportion over time [Figure 3] and [Supplementary Table 4]. | Table 2: Survival characteristics and length of hospital stay of the study sample
Click here to view |
 | Figure 3: Comparison of length of stay in hospital (days) for patient with acute congestive heart failure with urine output ≤2400 mL and >2400 mL in 1st 24 h
Click here to view |
| Discussion | | |
Despite the discovery of some novel therapeutics, diuretics are still considered as the backbone of therapy in the treatment plan for a CHF patient admitted to the hospital.[22] Furosemide is a loop diuretic and is the most widely utilized diuretic in clinical practice. As of yet no official guidelines exist for administering diuretics; doses, frequency, and route of administering diuretics vary greatly in clinical practice.
It is well-known that dose responses of diuretics can be unpredictable. Factors such as decreased bioavailability,[23] diuretic resistance,[24] and kidney dysfunction can cause inconsistent diuretic dose responses. The variations in the diuretic responses on urine output are important to consider because some previous studies (e.g., the DOSE trial) investigated the effect of the dose of diuretics on CHF outcomes without directly measuring the actual urine output. The assumption in such studies that diuretic doses always correlate with high urine outputs could have been potentially problematic because we understand that diuretic responses can be variable. In the backdrop of these concerns, we investigated the effect of the dose of furosemide on the first 24-h urine output in our study. We also analyzed the effect of renal function on the relationship of diuretic dose and urine output. The results of our study showed that higher doses of furosemide do result in higher urine outputs.
Furthermore, the renal function on presentation was an important factor in determining the response of diuretics; we found that the higher the creatinine, the higher the amount of diuretic dose needed to produce a given amount of urine output.
Another important factor that could potentially affect the efficacy of diuretics is concomitant use of other drugs such as nesiritide and dopamine (which are often given alongside furosemide in CHF); this was studied in the ROSE trial and the results showed no differences in urine outputs whether furosemide was used alone or when used along with dopamine or nesiritide.[25] Although the ROSE trial did not show any effect of other drugs on furosemide efficacy, a true effect might well exist in reality; we did not study the effect of concomitant use of dopamine or nesiritide on diuretic responses in our investigation. Future studies could take this factor into account in their analysis.
Overall the findings of our study indicate that although diuretic responses are inherently heterogeneous (due to multiple factors), the dose of diuretics correlates fairly well with urine outputs achieved and that renal function is an important measurable factor that can modify this relationship.
Intuitively, it makes sense that higher diuretic doses result in higher urine outputs and subsequently improved patient outcomes and a shorter hospital LOS. The results from previous studies however had shown mixed results and it was clear that the association of aggressive diuresis with improved outcomes needed further investigation.
The DOSE trial studied the effect of the dose of furosemide on LOS (as a secondary outcome); the results showed no difference in LOS with varying doses.[20]
The studies conducted by Howard and Dunn and Li and Hong used actual urine output to compare the effect of aggressive diuresis on LOS against nonaggressive diuresis; the results in these studies showed a shorter LOS in the aggressive diuresis group.[13],[21]
It is of note that each study mentioned above was unique and tried to gauge patient outcomes with its own methodology. Some studies used diuretic doses while others used direct urine output as a measure of diuresis. Not only were these studies inherently different but they also yielded contradicting results. Hence, we cannot draw any conclusion on best diuresis practices from the results of the studies mentioned above or from numerous other studies conducted previously.
Our investigation is uniquely placed in this complex milieu. We not only used direct urine output but also employed a specific strategy of early (initial 24 h of admission) aggressive diuresis to study its effects on hospital LOS. The results and analysis of our study showed that the hospital LOS was not affected when patients were put on aggressive diuresis in the first 24 h as compared to a nonaggressive strategy. These results are in line with the DOSE trial which also did not show a shorter LOS with aggressive diuresis.
The results of our study, although not surprising, do bring up the question of why did aggressive diuresis not result in a shorter LOS. Although there could many reasons, one possible explanation to the results is that the aggressive diuresis cohort in our study could have experienced a higher rate of adverse effects. There are some well-known complications of aggressive diuresis such as hypotension, electrolyte imbalance, or worsening renal function[26],[27],[28],[29],[30] documented in the literature. We hypothesize that the high rates of adverse effects in the aggressive diuresis cohort could have affected our results on two counts: first, they could have directly affected the LOS in the aggressive cohort; second, the high rates of side effects could have prompted the clinicians to adopt lower doses of diuretics after the initial 24 h, subsequently reducing the urine output even in the aggressive group after the initial 24 h, making the comparison of LOS with the nonaggressive group difficult. This fact that goes with the theory is that our study was not powered to detect statistical differences in adverse events between the two groups.
The results of our study should be interpreted in light of some limitations. First, the patients in this study represent a subset of the general CHF population (patients were selected from a single-center), this might have introduced a selection bias. Second, this study was not powered to detect statistical differences in adverse events between the groups that might have affected LOS in both groups. Third, our study focused only on the initial 24 urine output and did not take into account the urine output differences between the two groups for the entire LOS.
| Conclusion | | |
Early aggressive diuresis did not shorten the hospital LOS for patients admitted with CHF in our study. If future investigations can take into account the urine outputs for the entire hospital stay (instead of only the initial 24 h) and be powered to detect statistical differences in adverse events in the comparison groups, the effect of early aggressive diuresis on CHF patient outcomes can be better studied and possibly help unearth optimal diuresis practices.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Cook C, Cole G, Asaria P, Jabbour R, Francis DP. The annual global economic burden of heart failure. Int J Cardiol 2014;171:368-76.  |
| 2. | Ponikowski P, Anker SD, AlHabib KF, Cowie MR, Force TL, Hu S, et al. Heart failure: Preventing disease and death worldwide. ESC Heart Fail 2014;1:4-25. |
| 3. | Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, et al. Heart disease and stroke statistics-2017 Update. Circulation 2017;135:146-603. |
| 4. | Tumanan-Mendoza BA, Mendoza VL, Bermudez-Delos Santos AA, Punzalan FE, Pestanõ NS, Natividad RB, et al. Epidemiologic burden of hospitalisation for congestive heart failure among adults aged≥19 years in the Philippines. Heart Asia 2017;9:76-80. |
| 5. | Roger VL. Epidemiology of heart failure. Circ Res 2013;113:646-59. |
| 6. | Ng TP, Niti M. Trends and ethnic differences in hospital admissions and mortality for congestive heart failure in the elderly in Singapore, 1991 to 1998. Heart 2003;89:865-70. |
| 7. | Royston P, Altman DG, Fonarow GC, Adams KF, Abraham WT, Yancy CW, et al. Risk stratification for in-hospital mortality in acutely decompensated heart failure[2] (multiple letters). J Am Med Assoc 2005;293:2467-8. |
| 8. | Klein L, O'Connor CM, Leimberger JD, Gattis-Stough W, Piña IL, Felker GM, et al. Lower serum sodium is associated with increased short-term mortality in hospitalized patients with worsening heart failure: Results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study. Circulation 2005;111:2454-60. |
| 9. | McHugh MD, Ma C. Hospital nursing and 30-day readmissions among Medicare patients with heart failure, acute myocardial infarction, and pneumonia. Med Care 2013;51:52-9. |
| 10. | Wright SP, Verouhis D, Gamble G, Swedberg K, Sharpe N, Doughty RN. Factors influencing the length of hospital stay of patients with heart failure. Eur J Heart Fail 2003;5:201-9. |
| 11. | Kilgore M, Patel HK, Kielhorn A, Maya JF, Sharma P. Economic burden of hospitalizations of medicare beneficiaries with heart failure. Risk Manag Healthc Policy 2017;10:63-70. |
| 12. | Dallmann AC, Wilks A, Mattke S. Impact of event severity on hospital rankings based on heart failure readmission rates. Popul Health Manag 2019;22:243-7. |
| 13. | Howard PA, Dunn MI. Aggressive diuresis for severe heart failure in the elderly. Chest 2001;119:807-10. |
| 14. | Carles Trullàs J, Morales-Rull JL, Formiga F. Diuretic therapy in acute heart failure. Med Clin (Barc) 2014;142 Suppl 1:36-41. |
| 15. | Ellison DH, Felker GM. Diuretic treatment in heart failure-from physiology to clinical trials. Engl J Med 2017;377:1964. |
| 16. | Gheorghiade M, Pang PS. Acute heart failure syndromes. J Am Coll Cardiol 2009;53:557-73. |
| 17. | Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016;37:2129-200m. |
| 18. | Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Colvin MM, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of Amer. Circulation 2017;136:e137-61. |
| 19. | Vaduganathan M, Gheorghiade M. A roadmap to inpatient heart failure management. J Cardiol Jpn Coll Cardiol 2015;65:26-31. |
| 20. | Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med 2011;364:797-805. |
| 21. | Li JB, Hong HS. The value of aggressive diuretic therapy in acute decompensated stage of chronic heart failure. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2011;23:359-62. |
| 22. | Koniari K, Parissis J, Paraskevaidis I, Anastasiou-Nana M. Treating volume overload in acutely decompensated heart failure: Established and novel therapeutic approaches. Eur Heart J Acute Cardiovasc Care 2012;1:256-68. |
| 23. | Sica DA, Deedwania PC. Pharmacotherapy in congestive heart failure: Drug absorption in congestive heart failure: Loop diuretics. Congest Heart Fail 1998;4:37-43. |
| 24. | Brater DC. Resistance to loop diuretics. Why it happens and what to do about it. Drugs 1985;30:427-43. |
| 25. | Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, et al. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: The ROSE acute heart failure randomized trial. JAMA 2013;310:2533-43. |
| 26. | Cooper HA, Dries DL, Davis CE, Shen YL, Domanski MJ. Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction. Circulation 1999;100:1311-5. |
| 27. | Ahmad T, Jackson K, Rao VS, Tang WH, Brisco-Bacik MA, Chen HH, et al. Worsening renal function in patients with acute heart failure undergoing aggressive diuresis is not associated with tubular injury. Circulation 2018;137:2016-28. |
| 28. | Hasselblad V, Gattis Stough W, Shah MR, Lokhnygina Y, O'Connor CM, Califf RM, et al. Relation between dose of loop diuretics and outcomes in a heart failure population: Results of the ESCAPE trial. Eur J Heart Fail 2007;9:1064-9. |
| 29. | Testani JM, Chen J, McCauley BD, Kimmel SE, Shannon RP. Potential effects of aggressive decongestion during the treatment of decompensated heart failure on renal function and survival. Circulation 2010;122:265-72. |
| 30. | Joseph SM, Cedars AM, Ewald GA, Geltman EM, Mann DL. Acute decompensated heart failure: Contemporary medical management. Texas Heart Inst J 2009;36:510-20. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
|
